DESCRIPTION (Reproduced verbatim from the applicant's abstract): Diabetes eye complications are the leading cause of blindness in US adults aged 25-74. After 60+ years of debate as to the role of hyperglycemia in diabetes complications development, clinical trials demonstrated that reducing hyperglycemic exposure enormously reduces complication rate (Diabetes Control and Complications Trial (DCCT)). However, good blood glucose control does not eliminate retinopathic complications. This necessarily focuses diabetes research on development of additional treatments aimed not at diabetes control, but at prevention/treatment of specific complications. Laboratory research into the mechanisms of hyperglycemic damage and for development of new treatments to arrest these processes will be successful and clinical trials are an essential step in implementation of any new treatments. Clinical trials rely on prior identification of 1) at risk populations/tissues and 2) sensitive methods to monitor treatment effects. Our long-term research goal is to establish functional indicators of diabetic eye health and predictors of vision loss, and thus help in the prevention and treatment of the retinal complications of diabetes. Earlier we identified vision function changes that precede the development of retinopathy. In the current application period we showed that local ERGs show local changes corresponding to the local areas of visible diabetic retinopathic signs. Local correspondence of functional defects and local retinal damage hadn't been established using clinical visual field measures. Local areas of functional ERG loss are also evident in eyes without retinopathy. The research in the application proposes prediction of specific areas of future irreversible retinal damage based on local ERGs. We recently showed direct effects of acute glycemic levels on human vision function. We've shown that the FEOG is very sensitive to blood glucose fluctuations in both non-diabetics and diabetics. And, the diabetic FEOG appears to differ from that of the non-diabetic. The FEOG, a non-invasive objective measure of the eye's electrical response to light at the RPE/photoreceptor interface, reflects chloride transport by the retinal pigment epithelium. We will test the hypothesis that alterations in FEOG measures of RPE function precede retinopathy, and further, that FEOG measures in those with retinopathy and those with poor glycemic control differ from those of diabetics without retinopathy and with good control, respectively.